Josenilson Martins Pereira

Extensive investigation of a large Brazilian pedigree of 11778/haplogroup J Leber hereditary optic neuropathy

PURPOSE To conduct systematic epidemiologic, neuro-ophthalmologic, psychophysical, and mitochondrial DNA (mtDNA) genetic examinations on a newly identified pedigree with Leber hereditary optic neuropathy (LHON). DESIGN Observational population cohort study. METHODS A prospective investigation of an entire Brazilian LHON family. SETTING A field investigation by an international team conducted in a remote part of Brazil. STUDY POPULATION We evaluated 265 (both eyes) of the 328 living family members of this LHON pedigree. Only members of this pedigree were studied. Those entering the pedigree as spouses were used as controls. OBSERVATION PROCEDURES We conducted epidemiologic interviews emphasizing possible environmental risk factors, comprehensive neuro-ophthalmologic examinations, psychophysical tests, Humphrey visual field studies, fundus photography, and blood testing for mitochondrial genetic analysis. RESULTS We reconstructed a seven-generation maternal lineage descended from a common ancestor dating to the 1870s. All maternally related family members were invariably homoplasmic 11778 with a haplogroup J mtDNA, 33 being affected, of which 22 are still living. With each subsequent generation, there was a progressive decrease of penetrance, and only males were affected in the last two generations. A significant exposure (greater than 95% confidence intervals) to a variety of environmental risk factors characterized the affected individuals, with smoking as the most common (P <.01). Both affected and carriers (95% confidence intervals) presented with a significantly lower incidence of hypertension and high cholesterol compared with the control group (P <.05). CONCLUSIONS Almost 95% of a 328-living-member pedigree with LHON 11778/J haplogroup was comprehensively studied. Our initial results indicate the strong influence of environmental risk factors. The remarkably reduced incidence of cardiovascular risk in the maternal lineage is discussed. Further genetic analysis may reveal a role for the nuclear genome.

Estudo normativo do eletrorretinograma de campo total em adultos jovens

OBJETIVOS: A proposta deste estudo e estabelecer valores normativos para o eletrorretinograma (ERG) de campo total, em um grupo de voluntarios adultos jovens segundo o protocolo padrao recomendado pela Sociedade Internacional de Eletrofisiologia Visual Clinica (ISCEV). METODOS: Participaram deste estudo 42 voluntarios normais com idades variando de 15 a 26 anos, sendo 20 homens e 22 mulheres. Os eletrorretinogramas de campo total foram obtidos com eletrodos de lente de contato bipolares e seguiram as 5 etapas do protocolo da Sociedade Internacional de Eletrofisiologia Visual Clinica: a) resposta de bastonetes; b) reposta maxima; c) potenciais oscilatorios; d) resposta maxima de cones; e) resposta de cones ao flicker 30 Hz. Os parâmetros analisados foram a amplitude de resposta do pico da onda-a ate o pico da onda-b (pico a pico em mV) e o tempo de culminacao da onda-b (ms). RESULTADOS: As medias (± 1 desvio padrao) da amplitude pico a pico foram: resposta de bastonetes - 241,1 ± 66,9 µV; resposta maxima - 385,4 ± 71,8 µV; potenciais oscilatorios - 180,6 ± 48,6 µV; resposta de cones -102,8 ± 36,3 µV e flicker 30 Hz - 69,2 ± 26,6 µV. Para o tempo implicito da onda-b os valores foram: resposta de bastonetes - 85,2 ± 7,6 ms; resposta maxima -45,6 ± 2,0ms; resposta de cones - 27,8 ± 1,2ms e flicker 30 Hz - 27,9 ± 1,2 ms. Os resultados foram comparaveis entre os grupos masculino e feminino, exceto para a resposta maxima em que as mulheres obtiveram amplitudes estatisticamente maiores (t=2,06; P=0,046). CONCLUSAO: Os valores encontrados estao de acordo com dados normativos da literatura e sao fundamentais para o diagnostico correto de disfuncoes retinianas em pacientes na mesma faixa etaria. Inclusao de outras faixas etarias e o aumento no numero de sujeitos testados sao necessarios para estender valores normativos para o eletrorretinograma.

Age norms for monocular grating acuity measured by sweep-VEP in the first three years of age

PURPOSE To determine age norms for grating visual acuity and interocular acuity differences measured by the sweep-visually evoked potentials (VEP) technique in the first three years of life. METHODS Monocular grating visual acuity was measured using the sweep-VEP in 67 healthy normal infants and children in the first 36 months of life. RESULTS Sweep-VEP grating acuity ranged from 0.80 logMAR (20/125 Snellen equivalent) in the first month of life to 0.06 logMAR (20/20 Snellen equivalent) at 36 months of age. Lower normal limits (95th percentile limit) ranged from 0.95 logMAR (20/180) to 0.12 logMAR (20/25) with a progression of approximately 3 octaves in the first 36 months of age. The largest acceptable interocular acuity difference for clinical purposes was 0.10 logMAR. CONCLUSIONS Age norms for grating acuity along with interocular acuity differences were determined using the sweep-VEP technique. These norms should be incorporated in clinical practice for precise diagnosis of visual status in infants and preverbal children.

Sweep visually evoked potentials and visual findings in children with West syndrome

BACKGROUND West syndrome (WS) is a type of early childhood epilepsy characterized by progressive neurological development deterioration that includes vision. AIM To demonstrate the clinical importance of grating visual acuity thresholds (GVA) measurement by sweep visually evoked potentials technique (sweep-VEP) as a reliable tool for evaluation of the visual cortex status in WS children. METHODS This is a retrospective study of the best-corrected binocular GVA and ophthalmological features of WS children referred for the Laboratory of Clinical Electrophysiology of Vision of UNIFESP from 1998 to 2012 (Committee on Ethics in Research of UNIFESP n° 0349/08). The GVA deficit was calculated by subtracting binocular GVA score (logMAR units) of each patient from the median values of age norms from our own lab and classified as mild (0.1-0.39 logMAR), moderate (0.40-0.80 logMAR) or severe (>0.81 logMAR). Associated ophthalmological features were also described. RESULTS Data from 30 WS children (age from 6 to 108 months, median = 14.5 months, mean ± SD = 22.0 ± 22.1 months; 19 male) were analyzed. The majority presented severe GVA deficit (0.15-1.44 logMAR; mean ± SD = 0.82 ± 0.32 logMAR; median = 0.82 logMAR), poor visual behavior, high prevalence of strabismus and great variability in ocular positioning. The GVA deficit did not vary according to gender (P = .8022), WS type (P = .908), birth age (P = .2881), perinatal oxygenation (P = .7692), visual behavior (P = .8789), ocular motility (P = .1821), nystagmus (P = .2868), risk of drug-induced retinopathy (P = .4632) and participation in early visual stimulation therapy (P = .9010). CONCLUSIONS The sweep-VEP technique is a reliable tool to classify visual system impairment in WS children, in agreement with the poor visual behavior exhibited by them.

Amblyopia after unilateral infantile cataract extraction after six weeks of age

PURPOSE To determine interocular grating acuity difference in children treated for unilateral infantile cataract. METHODS A group of 27 children previously treated for unilateral infantile cataract, had their monocular visual acuity measured by sweep visual evoked potentials. Interocular grating acuity difference was calculated as the absolute subtraction of monocular acuity scores. Lens status, opacity severity and eye alignment were considered for analysis. RESULTS Mean interocular grating acuity difference obtained from unilateral cataract patients was 0.58 +/- 0.20 logMAR. This result was significantly larger than 0.10 logMAR used as normative data. Children with severe opacities had a more pronounced amblyopia than the moderate ones. No significant correlation between amblyopia and strabismus or aphakia was found. CONCLUSIONS Interocular acuity difference in this group of unilateral congenital cataract was more pronounced than previous reports, mainly because of delay in diagnosis, surgery and optical correction.

Steady-state sweep visual evoked potential processing denoised by wavelet transform

Visually evoked potential (VEP) is a very small electrical signal originated in the visual cortex in response to periodic visual stimulation. Sweep-VEP is a modified VEP procedure used to measure grating visual acuity in non-verbal and preverbal patients. This biopotential is buried in a large amount of electroencephalographic (EEG) noise and movement related artifact. The signal-to-noise ratio (SNR) plays a dominant role in determining both systematic and statistic errors. The purpose of this study is to present a method based on wavelet transform technique for filtering and extracting steady-state sweep-VEP. Counter-phase sine-wave luminance gratings modulated at 6 Hz were used as stimuli to determine sweep-VEP grating acuity thresholds. The amplitude and phase of the second-harmonic (12 Hz) pattern reversal response were analyzed using the fast Fourier transform after the wavelet filtering. The wavelet transform method was used to decompose the VEP signal into wavelet coefficients by a discrete wavelet analysis to determine which coefficients yield significant activity at the corresponding frequency. In a subsequent step only significant coefficients were considered and the remaining was set to zero allowing a reconstruction of the VEP signal. This procedure resulted in filtering out other frequencies that were considered noise. Numerical simulations and analyses of human VEP data showed that this method has provided higher SNR when compared with the classical recursive least squares (RLS) method. An additional advantage was a more appropriate phase analysis showing more realistic second-harmonic amplitude value during phase brake.

Validation of a new fiber electrode prototype for clinical electroretinography

PURPOSE To validate a new fiber electrode prototype for clinical electroretinography (ERG). METHODS A recently developed prototype of a disposable reference-coupled fiber electrode (patent pending Brazilian Institute of Industrial Property # PI0602186-7), including one fiber for corneal signals and a second fiber acting as reference was tested in a group of 20 healthy volunteers (17-31 years; mean 22.7 +/- 4.5; 8 males). Standard electroretinography rod and cone responses were recorded from a fully dilated pupil simultaneously in both eyes with a reference-coupled fiber electrode prototype in one randomly assigned eye and a DTL electrode in the other eye after 30 min of dark-adaptation. After presenting dark- and light-adapted stimuli, each response was analyzed for a- and b-wave amplitude and implicit time. The VERIS 5.1.9 system was used for electroretinography data acquisition and analysis. Electroretinography outcomes were analyzed by Mann-Whitney test. Slit-lamp examination was performed in both eyes right after electroretinography session to evaluate possible adverse effects. RESULTS Responses recorded with reference-coupled fiber electrode prototypes were comparable to commercially available DTL fiber electrodes. On a qualitative analysis, reference-coupled fiber electrodes provided recordings with less amount of noise. On average, scotopic electroretinography amplitude and b-wave implicit time recorded using DTL were, respectively, 287.6 microV and 36.3 ms with similar findings for the reference-coupled fiber electrode prototype (287.9 microV and 36.3 ms). Under photopic conditions DTL mean amplitude and implicit time were, respectively 108.9 microV and 24.5 ms with similar results for the reference-coupled fiber electrodes prototypes (116.4 microV and 24.5 ms). No corneal abrasions or any other significant adverse effects were found after electroretinography recording with both electrodes. CONCLUSIONS The reference-coupled fiber electrode prototype provided stable and safe recordings of corneal electroretinograms compared to the commercially availabe DTL electrode in healthy human subjects. The prototype is a feasible alternative instrument for clinical electroretinography recording to assess retinal function, however further analysis is recommended to validate its clinical usefulness in patients with retinal disorders.

Acuidade visual e função de bastonetes em pacientes com retinose pigmentária

PURPOSE: To investigate visual acuity and rod function, and correlate them to different clinical parameters in patients with retinitis pigmentosa (RP). METHODS: A cohort of 199 patients with retinitis pigmentosa (110 males and 89 females), aged 6-79 years (mean = 36.8±17.5) had their monocular visual acuity measured by the ETDRS chart and rod function assessed by full-field electroretinogram and dark-adapted thresholds. The distribution of different genetic subtypes of retinitis pigmentosa was 20.3% autosomal dominant, 14.2% X - linked, 24.2% autosomal recessive and 41.3% isolated. History of consanguinity was found in 41 (20.6%) patients. Forty-one patients (20.6%) were 20 years old or less, 77 (38.6%) ranged from 21 - 40 years, 61 (30.7%) from 41 - 60 years, and 20 (10.1%) were 61 years or older. Peak-to-peak amplitude and b-wave implicit time were measured and statistically analyzed (one-way ANOVA). Pearson correlation was performed between rod amplitude and dark-adapted thereshold and rod amplitude and visual acuity. RESULTS: Analyzing the visual acuity data according to genetic subtypes, without considering age, showed that as a group, patients with autosomal recessive and isolated retinitis pigmentosa have less severe impairment of visual acuity, than those with X-linked retinitis pigmentosa. Nyctalopia begun earlier in X-linked groups, compared with the remaining groups (p=0.011). A negative correlation was found between dark-adapted thereshold and scotopic rod amplitude (Pearson correlation coefficient = - 0.772 and P =0.000). There were no significant relationships between visual acuity and rod response by electroretinogram (Pearson correlation coefficient = 0.0815 and P = 0.286), P > 0.050. CONCLUSIONS: In a cohort of retinitis pigmentosa patients, 31.2% had vision of 20/40 or better. Rod function loss was highly correlated when assessed electrophysiologically (ERG) and psychophysically (dark-adapted thershold). No correlation was found between rod response measured by electroretinogram and visual acuity.

Full-field electroretinogram recorded with skin electrodes in normal adults

Purpose: Alternative recording methods have been tested to allow the electroretinogram (ERG) recording in uncooperative patients and/or patients with palpebral alterations, including recordings with skin electrodes. The purpose of this study was to compare ERG recorded with skin electrodes and well-established microfiber electrodes and to determine normative values of ERG parameters for recording with skin electrodes. Methods: Fifty healthy volunteers (17-26 years; mean 20.63 ± 2.01 years) participated in the study. A gold disk skin electrode was placed on the lower orbital rim of a randomly chosen eye. On the contralateral eye, a microfiber electrode was positioned in the lower conjunctival sac. Gold disc electrodes were positioned at the ipsilateral outer canthus of both eyes acting as reference electrodes for the creation of a potential difference. Two ground electrodes were placed on the lobe of each ear. ERGs were recorded according to the International Society of Clinical Electrophysiology Visual (ISCEV) protocol using the VERIS 5.1.9 system for data acquisition and analysis. Results: Both types of electrodes showed similar wave response morphologies. The implicit time of responses between the two electrodes was comparable. On peak-to-peak amplitude, skin electrode recordings showed an amplitude reduction of 61.4% for rod responses, 61.5% for maximal responses, 46.2% for oscillatory potentials, 57.4% for cone responses, and 54.4% for 30Hz-flicker responses, when compared with microfiber electrode recordings. Based on these findings, normative values for peak-to-peak amplitude and implicit time to be used as a reference for ERGs recorded with skin electrodes were determined. Conclusions: ERGs recorded with skin electrodes presented lower peak-to-peak amplitude compared with microfiber electrodes. However, using appropriate normative values, skin electrodes may be useful for specific target populations such as uncooperative infants and/or patients with ocular surface alterations.

Acuidade visual e eletrorretinografia de campo total em pacientes com síndrome de Usher

PURPOSE: Ushers syndrome (US) is a group of genetically distinct autossomal conditions, characterized by sensorineural hearing loss accompanied by a retinal dystrophy indistinguishable from retinitis pigmentosa (RP). The purpose of this study was to analyze full-field electroretinography (ERG) and visual acuity (VA) among patients with type I and II Ushers syndrome. METHODS: Electroretinography responses and visual acuity were studied in 22 patients (mean age at test = 26.8±16.8 years). Seventeen patients had SU type I and 5 patients were diagnosed as Ushers syndrome type II. RESULTS: Mean visual acuity was 0.9 logMAR (20/160, Snellen equivalent) for patients with Ushers syndrome type I and 0.4 logMAR (20/50, Snellen equivalent) for patients with Ushers syndrome type II. Scotopic rod and maximal responses were non-detectable in both groups. Mean amplitude for oscillatory potentials was 14.5 µV ±6.1 in Ushers syndrome type I and 12.6 µV±5.2 in Ushers syndrome type II. Cone responses were non-detectable in 95% of the patients with Ushers syndrome I and in 100% of patients with Ushers syndrome II. Mean amplitude for 30 Hz flicker photopic cone response was 3.1 µV±4.1 for Ushers syndrome type I and 1.0 µV±0.6 for type II with mean implicit time of 34.0 ms±6.2 (US I) and 35.8 ms±3.1 (type II). CONCLUSIONS: Visual acuity was relatively preserved in both groups, however Ushers syndrome II group showed better visual acuity results. Electroretinography findings were severely reduced in both groups, with most patients showing non-detectable rod and cone responses.